2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2008040435v1 20/11/2389    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bastos, A. P. Articles by Onuchic, L. F. PubMed PubMed Citation Articles by Bastos, A. P. Articles by Onuchic, L. F. Related Collections Related Article

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Ana P. Bastos^*, Klaus Piontek, Ana M. Silva, Dino Martini, Luis F. Menezes, Jonathan M. Fonseca^*, Ivone I. Fonseca^*, Gregory G. Germino and Luiz F. Onuchic^*

*Department of Medicine, Division of Nephrology, and
Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil;
Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland; and
Division of Pathology, Beneficência Portuguesa Hospital, São Paulo, Brazil

Correspondence: Dr. Luiz F. Onuchic, Avenida Dr. Arnaldo, 455, Sala 4304, São Paulo, SP 01246-903, Brazil. Phone: 55-11-3061-8399; Fax: 55-11-3061-8361; E-mail: lonuchic{at}lim12.fm.usp.br

Received for publication April 29, 2008. Accepted for publication August 6, 2009.

Mutations in PKD1 cause the majority of cases of autosomal dominant polycystic kidney disease (ADPKD). Because polycystin 1 modulates cell proliferation, cell differentiation, and apoptosis, its lower biologic activity observed in ADPKD might influence the degree of injury after renal ischemia/reperfusion. We induced renal ischemia/reperfusion in 10- to 12-wk-old male noncystic Pkd1^+/– and wild-type mice. Compared with wild-type mice, heterozygous mice had higher fractional excretions of sodium and potassium and higher serum creatinine after 48 h. In addition, in heterozygous mice, also cortical damage, rates of apoptosis, and inflammatory infiltration into the interstitium at time points out to 14 d after injury all increased, as well as cell proliferation at 48 h and 7 d. The mRNA and protein expression of p21 was lower in heterozygous mice than wild-type mice at 48 h. After 6 wk, we observed dilated tubules, microcysts, and increased renal fibrosis in heterozygotes. The early mortality of heterozygotes was significantly higher than that of wild-type mice when we extended the duration of ischemia from 32 to 35 min. In conclusion, ischemia/reperfusion induces a more severe injury in kidneys of Pkd1-haploinsufficient mice, a process that apparently depends on a relative deficiency of p21 activity, tubular dilation, and microcyst formation. These data suggest the possibility that humans with ADPKD from PKD1 mutations may be at greater risk for damage from renal ischemia/reperfusion injury.

Related Article

This Month's Highlights
J. Am. Soc. Nephrol. 2009 20: A12. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673